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Ionic Liquid-Based Transcutaneous Peptide Antitumor Vaccine: Therapeutic Effect in a Mouse Tumor Model

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Abstract

Traditional vaccinations need to be injected with needles, and since some people have a strong aversion to needles, a needle-free alternative delivery system is important. In this study, we employed ionic liquids (ILs) for transcutaneous delivery of cancer antigen-derived peptides to obtain anticancer therapeutic effects in a needle-free manner. ILs successfully increased the in vitro skin permeability of a peptide from Wilms tumor 1 (WT1), one of the more promising cancer antigens, plus or minus an adjuvant, resiquimod (R848), a toll-like receptor 7 agonist. In vivo studies demonstrated that concomitant transcutaneous delivery of WT1 peptide and R848 by ILs induced WT1-specific cytotoxic T lymphocyte (CTL) in mice, resulting in tumor growth inhibition in Lewis lung carcinoma-bearing mice. Interestingly, administrating R848 in ILs before WT1 peptides in ILs increased tumor growth inhibition effects compared to co-administration of both. We found that the prior application of R848 increased the infiltration of leukocytes in the skin and that subsequent delivery of WT1 peptides was more likely to induce WT1-specific CTL. Furthermore, sequential immunization with IL-based formulations was applicable to different types of peptides and cancer models without induction of skin irritation. IL-based transcutaneous delivery of cancer antigen-derived peptides and adjuvants, either alone or together, could be a novel approach to needle-free cancer therapeutic vaccines.

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Acknowledgements

We thank Professor Emerita Theresa M. Allen for helpful editorial comments.

Funding

This study was in part supported by JSPS, a Grant-in-Aid for Exploratory Research (18K19925), AMED under Grant Number JP21ak0101175, and by a research program for the development of an intelligent Tokushima artificial exosome (iTEX) from Tokushima University.

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Authors and Affiliations

  1. Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University, 1-78-1, Sho-Machi, Tokushima, 770-8505, Japan

    Taro Shimizu, Takaaki Matsuzaki, Shoichiro Fukuda, Chihiro Yoshioka, Yuna Shimazaki, Shunsuke Takese, Hidenori Ando, Yu Ishima & Tatsuhiro Ishida

  2. MEDRx Co., Ltd, 431-7 Nishiyama, Higashikagawa City, Kagawa, 769-2712, Japan

    Katsuhiro Yamanaka, Takashi Nakae, Masaki Ishibashi & Hidetoshi Hamamoto

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  1. Taro Shimizu
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Contributions

T.S.: conceptualization, data curation, formal analysis, methodology, project administration, visualization, and roles/writing—original draft; T.M.: data curation, formal analysis, investigation, methodology, and validation; S.F.: data curation, formal analysis, investigation, methodology, and validation; C.Y.: data curation, formal analysis, investigation, methodology, and validation; Y.S.: data curation, formal analysis, investigation, methodology, and validation; S.T.: data curation, formal analysis, investigation, methodology, and validation; K.Y.: data curation, formal analysis, investigation, methodology, and validation; T.N.: data curation, formal analysis, investigation, methodology, and validation; M.I.: data curation, formal analysis, investigation, methodology, and validation; H.H.: conceptualization, project administration, resources, and writing—review and editing; H.A.: writing—review and editing; Y.I.: writing—review and editing; T.I.: conceptualization, funding acquisition, writing—review and editing, and supervision.

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Correspondence to Taro Shimizu or Tatsuhiro Ishida.

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Conflict of Interest

K.Y., T.N., M.I., and H.H. are employees of MEDRx Co., Ltd. The authors report no other conflicts of interest in this work.

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Shimizu, T., Matsuzaki, T., Fukuda, S. et al. Ionic Liquid-Based Transcutaneous Peptide Antitumor Vaccine: Therapeutic Effect in a Mouse Tumor Model. AAPS J 25, 27 (2023). https://doi.org/10.1208/s12248-023-00790-w

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